Seeking for Regulatory Mechanisms of Phospholamban Expression

Abstract

In this issue of Circulation Research, Ren et al13 introduced a novel transcription factor involved in the regulation of PLN expression, ZBTB20. ZBTB20 is a member of the broad complex, Tramtrack, and bric-a-brac and POZ (poxvirus and zinc finger) family of transcriptional repressors. ZBTB20 is involved in the regulation of various biological processes in different tissues, such as cellular proliferation and differentiation, glucose and lipid metabolism, inflammation, tissue repair, and oncogenesis.Due to its versatility, global knockout mice lacking ZBTB20 exhibit mortality within the first month of age.14 Up to day 16 postpartum, besides hypotension, the transgenic mice display defects in cardiac development and contractility, suggesting a potential cardiac role of ZBTB20. In the current study, Ren et al13 go a step further in exploring the importance of this transcription factor in cardiac function by generating a mouse model with cardiomyocyte-specific ablation of ZBTB20. These mice exhibited normal heart development but showed an increase in basal contractility and SERCa2a activity, attributed to a reduction in PLN expression. The results identify ZBTB20 as a novel transcription factor implicated in the regulation of PLN expression. Unfortunately, it was somewhat disappointing to find that the promoter region of the PLN gene lacks ZBTB20 binding sites. Therefore, additional investigation will be required to understand the mechanism by which ZBTB20 controls PLN expression.